Background: Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation. Objective: This study evaluated the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, for coronavirus disease 2019. Methods: We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe coronavirus disease 2019. Results: Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus standard-of-care treatment (22 patients) or placebo based on standard-of-care treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study. Treatment with ruxolitinib plus standard-of-care was not associated with significantly accelerated clinical improvement in severe patients with coronavirus disease 2019, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed computed tomography improvement at day 14 compared with 13 (61.9%) patients from the control group (P 5 .0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at day 28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group. Conclusions: Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest computed tomography improvement, a faster recovery from lymphopenia, and favorable side-effect profile in the ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population. (

COVID-19 is a disease with heterogeneous clinical appearances. Most patients are asymptomatic or exhibit mild to moderate symptoms; approximately 15% progress to severe pneumonia and about 5% are eventually admitted to the intensive care unit (ICU) due to acute respiratory distress syndrome (ARDS), septic shock and/ or multiple organ failure. ICU patients respond poorly to currently available treatments and exhibit a high mortality rate. 1-3 Inadequate identification of the determinants of fatal outcomes is one of the major obstacles to the improvement of the outcomes in severe COVID-19 patients. A previous study reported a scoring system (COVID-GRAM) which accurately predicted the occurrence of critical illness in hospitalized COVID-19 patients. 4 Damage-associated molecular patterns (DAMPs), or alarmins, are a number of molecules, released by stressed cells undergoing microbial infection or sterile injury, that act as danger signals to promote and exacerbate the inflammatory response. 5,6 Of note, the serum level of S100A8/A9 and HMGB1 was found to be correlated with both the severity of pathogen-associated tissue damage and excessive cytokine storm. 7 Despite the hypothesis that S100A8/A9 and HMGB1 are significantly involved in COVID-19, so far, no study has yet tried to substantiate the hypothesis. In this study, we aimed to define the role of S100A8/ A9 and HMGB1 in progression to a fatal outcome and develop clinically relevant risk strata for COVID-19 patients. A total of 121 patients were enrolled in this retrospective study, of which 40 patients were in ICU and 81 patients in general wards at enrollment (Table S1). ICU Patients had much higher COVID-GRAM risk scores in comparison to those in general wards. Complications, including ARDS, sepsis, septic shock, secondary infection, acute renal injury, acute cardiac injury or failure, were more frequent in CCOVID-19 patients admitted to ICU. As of the cutoff date of April 30, 2020, most of non-ICU patients (96.3%) had been discharged alive, while 82.5% of ICU patients had died in ICU.

Active learning aims to select a small subset of data for annotation such that a classifier learned on the data is highly accurate. This is usually done using heuristic selection methods, however the effectiveness of such methods is limited and moreover, the performance of heuristics varies between datasets. To address these shortcomings, we introduce a novel formulation by reframing the active learning as a reinforcement learning problem and explicitly learning a data selection policy, where the policy takes the role of the active learning heuristic. Importantly, our method allows the selection policy learned using simulation on one language to be transferred to other languages. We demonstrate our method using cross-lingual named entity recognition, observing uniform improvements over traditional active learning.

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B1 cells are evolutionarily conserved innate-like cells that share many features with macrophages. It has also been established that B1 cells have a close developmental relationship with macrophages. However, whether B1 cells are able to act as professional phagocytic cells is not clear. In this study, we report that mouse peritoneal cavity (PerC) B cells demonstrate in vivo and in vitro phagocytic activities for Staphylococcus aureus, Escherichia coli, and polystyrene fluorescent microspheres. Approximately 5% of PerC B cells, mainly B1b cells, showed phagocytic activity. Ingested microbes were killed efficiently in the phagolysosome. The antigen-specific B-cell antigen receptor promoted B-cell phagocytosis, resulting in antigen presentation to T cells after uptake of bacteria. Our results reveal for the first time that mouse B1 cells have active phagocytic capabilities and thereby act as a bridge linking innate and adaptive immunity.

The China Assessment of Antifungal Therapy in Hematological Disease study, the first large-scale observational study of invasive fungal disease (IFD) in China, enrolled 1401 patients undergoing hematopoietic stem cell transplantation (HSCT) (75.2% allogeneic and 24.8% autologous) at 31 hospitals across China. The overall incidence of proven or probable IFD was 7.7% (108 of 1401); another 266 cases (19.0%) were possible IFD. After allogeneic or autologous HSCT, the incidence of proven/probable IFD was 8.9% (94 of 1053) and 4.0% (14 of 348), respectively. Some cases (14 of 108) developed during conditioning before transplantation. The cumulative incidence of proven/probable IFD increased steeply in the first month after transplantation and after 6 months, the incidence was significantly higher in allogeneic than it was in autologous transplant recipients (9.2% versus 3.5%; P = .001) and when stem cells were derived from cord blood or bone marrow and peripheral blood (P = .02 versus other sources). Independent risk factors for proven/probable IFD in allogeneic HSCT were diabetes, HLA-matched unrelated donor, prolonged severe neutropenia (absolute neutrophil count > 500/mm(3) for >14 days), and immunosuppressants (odds ratio, 2.0 to 3.4 for all). Antifungal prophylaxis was independently protective (P = .01). Previous IFD and prolonged severe neutropenia were significant independent risk factors among autologous transplantation patients (P < .01, P = .04, respectively). In total, 1175 (83.9%) patients received antifungal prophylaxis (91.6% triazoles) and 514 (36.7%) were treated in the hospital with therapeutic antifungals (89.1% triazoles; median 27 days). Empirical, pre-emptive, and targeted antifungals were used in 82.3%, 13.6%, and 4.1% of cases, respectively. Overall mortality (13.4%; 188 deaths) was markedly higher in patients with proven (5 of 16; 31.3%), probable (20 of 92; 21.7%), or possible (61 of 266; 22.9%) IFD; allogeneic (171 of 1053; 16.2%) rather than autologous (17 of 348; 4.9%) HSCT and was significantly higher in patients receiving pre-emptive (18.6%) rather than empirical (6.1%) or targeted (9.5%) antifungal therapy (P = .002). Improvements in the selection and timing of prophylactic antifungals would be welcome. Health care providers should remain alert to the increased risk of IFD and associated mortality in allogeneic HSCT recipients and the ongoing risk of IFD even after discharge from the hospital.

The object of the study is to identify N-glycan profiling changes associated with gastric cancer and explore the impact of core-fucosylation on biological behaviors of human gastric cancer cells. A total of 244 subjects including gastric cancer, gastric ulcer and healthy control were recruited. N-glycan profiling from serum and total proteins in gastric tissues was analyzed by DNA sequencer-assisted fluorophore-assisted capillary electrophoresis. The abundance of total core-fucosylated residues and the expression of enzymes involved in core-fucosylation were analyzed with lectin blot, quantitative reverse transcription-polymerase chain reaction, western blot, Immunohistochemical staining and lectin-histochemical staining. The recombinant plasmids of GDP-fucose transporter and α-1,6-fucosyltransferase (Fut8) were constructed and transfected into gastric cancer cell lines BGC-823 and SGC-7901. CCK-8 and wound healing assay were used to assess the functional impact of core-fucosylation modulation on cell proliferation and migration. Characteristic serum N-glycan profiles were found in gastric cancer. Compared with the healthy control, a trianntenary structure abundance, peak 9 (NA3Fb), was increased significantly in gastric cancer, while the total abundance of core-fucosylated residues (sumfuc) was decreased. Core-fucosylated structures, peak6(NA2F) and peak7(NA2FB) were deceased in gastric tumor tissues when compared with that in adjacent non-tumor tissues. Consistently, lens culinaris agglutinin (LCA)-binding proteins were decreased significantly in sera of gastric cancer, and protein level of Fut8 was decreased significantly in gastric tumor tissues compared with that in adjacent non-tumor tissues. Upregulation of GDP-Tr and Fut8 could inhibit proliferation, but had no significant influence on migration of BGC-823 and SGC-7901 cells. Core-fucosylation is down regulated in gastric cancer. Upregulation of core-fucosylation could inhibit proliferation of the human gastric cancer cells.

Key Points• Chinese patients with newly diagnosed CML-CP achieved higher rates of MMR with nilotinib vs imatinib.• Nilotinib was well tolerated, and no new safety signals were observed.Treatment with a tyrosine kinase inhibitor (TKI) targeting BCR-ABL1 is currently the standard of care for patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP).In this study, we present results of the ENESTchina (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-China) that was conducted to investigate nilotinib 300 mg twice daily vs imatinib 400 mg once daily in a Chinese population. ENESTchina met its primary end point with a statistically significant higher rate of major molecular response (MMR; BCR-ABL1 £0.1% on the International Scale) at 12 months in the nilotinib arm vs the imatinib arm (52.2% vs 27.8%; P < .0001), and MMR rates remained higher with nilotinib vs imatinib throughout the follow-up period. Rates of complete cytogenetic response (0% Philadelphia chromosome-positive [Ph1] metaphases by standard cytogenetics) were comparable and ‡80% by 24 months in both arms. The estimated rate of freedom from progression to accelerated phase/blast crisis at 24 months was 95.4% in each arm. The safety profiles of both drugs were similar to those from previous studies. In conclusion, rates of MMR at 12 months were superior with nilotinib vs imatinib in Chinese patients with newly diagnosed Ph1 CML-CP. This trial was registered at www.clinicaltrials.gov as #NCT01275196. (Blood. 2015;125(18):2771-2778